Biomedical subjects

D L Morris

Publications and source records attributed to D L Morris.

At least 19 recordsLinked to original sources

PubMed1992

Distal metacarpal sequestration in a bison.

A 2-year-old 400-kg female American bison was admitted for evaluation and treatment of an open fracture of the right metacarpal bones 3 and 4. Radiography revealed osteolysis of the distal metaphysis and epiphysis, with extensive bony callus formation along the dorsoproximal and proximomedial aspects extending distally to the proximomedial aspect of the proximal phalanx. Evidence of periosteal or bony proliferation at the fracture site or along the distal segment of the third and fourth metacarpal bones was not visible, suggesting that the distal fracture fragment was becoming a sequestrum. Treatment consisted of soft tissue debridement and placement of the limb in a full-limb cast. The cast was changed every 4 weeks until the sequestrum was removed and the bone healed. It is rare for the distal half of a long bone to sequester following fracture. Additionally, it is remarkable that the sequestrum served as a buttress, which prevented collapse of the bone until the sequestrum was replaced by functional bony callus.

Animals↗

PubMed1992

SMS 201.995 inhibits in vitro and in vivo growth of human colon cancer.

The effect of a long-acting somatostatin analogue SMS 201.995 (SMS; Sandoz) on basal and gastrin-stimulated growth of 4 human colon cancer lines was studied in vitro and in vivo. Proliferation assay was done with overnight [75Se]selenomethionine uptake after 5 days of incubation. Gastrin concentrations used were 5e-10 M and 1e-7 M. SMS concentrations were from 2e-12 M to 2e-7 M. Cell lines LIM 1215, LIM 2405, and LIM 2412 were inhibited dose-dependently in both basal and gastrin-stimulated groups. LIM 1863 was slightly stimulated. Based on in vivo growth characteristics, LIM 2412 and LIM 2405 were selected for xenograft study. The dose of 50 micrograms/kg/day was arrived at after a preliminary experiment showed it to be safe and effective. The LIM 2412 xenografts in the SMS-treated animals were 473.3 +/- 99.9 (SD) versus 838.1 +/- 111.3 mm3 in control (P less than 0.05) after 20 days. The LIM 2405 tumors were also significantly inhibited (81.2 +/- 30.0 versus 245.7 +/- 48.3 mm3, P less than 0.01). The effect of SMS appeared to be reversible. Oral SMS at 200 micrograms/kg/day was not absorbed. This study suggests that SMS may have direct antitumor effects in human colon cancer.

Animals↗

PubMed1992

Predeposit autologous blood transfusion in patients with colorectal cancer: a feasibility study.

Over a 2-year period, a predeposit autologous blood transfusion service was provided for all patients undergoing elective surgery for left-sided colonic or rectal cancer in one hospital. Of 129 such patients, 28 were suitable for autologous donation. Eight of these received autologous blood only, 13 required no transfusion, and seven needed additional homologous blood. Thus, although predeposit autologous transfusion for patients with colorectal cancer is possible, only a very small proportion are likely to derive any benefit which it might confer.

Aged↗

PubMed1992

Coumarin inhibits micronuclei formation induced by benzo(a)pyrene in male but not female ICR mice.

Coumarin has been shown to be an effective inhibitor of carcinogenesis in rodents if given before and during the carcinogen treatment. We investigated the possibility that pretreatment with coumarin would inhibit the genotoxicity of benzo(a)pyrene (BP) in ICR mice as indicated by the bone marrow micronucleus test, a widely used in vivo test for genotoxicity. Our studies showed that pretreatment of male mice with doses of coumarin at 65 or 130 mg/kg/day for 1 week (with 1 day of no treatment at midweek) partially inhibited the genotoxicity of BP at a single intraperitoneal dose of 150 mg/kg. Time course experiments showed a decrease in induced micronuclei in the bone marrow at several time points after the BP treatment, thus indicating a true inhibition and not a lag in the induction of micronuclei. However, no inhibition in micronuclei formation was seen in female mice pretreated with the same doses of coumarin. Coumarin treatment alone did not induce micronuclei in either sex. Future studies are needed to analyze the mechanisms responsible for the difference noted between the sexes.

Animals↗

PubMed1992

The mutagenic effects of low level sub-acute inhalation exposure to benzene in CD-1 mice.

Benzene is a widely used chemical and common environmental contaminant. It is carcinogenic in man and animals and is genotoxic in mice, rats, and occupationally exposed humans at doses above one part per million. In order to evaluate the genotoxic effects of prolonged exposures to very low concentrations of benzene, we exposed CD-1 mice to benzene by inhalation for 22 h per day, seven days per week for six weeks at 40, 100 and 1000 parts per billion (ppb). Additional groups were exposed to purified air or were housed in standard plastic cages. The effects of in vivo exposure to benzene were evaluated by using an autoradiographic assay to determine the frequency of mutants which represent mutations at the hypoxanthine-guanine phosphoribosyl transferase (hprt) locus in spleen lymphocytes. At the end of the six weeks exposure period lymphocytes were recovered from the spleens of the mice and cryopreserved prior to assay. Mutant cells were selected on the basis of their ability to incorporate tritiated thymidine in the presence of 6-thioguanine. The weighted mean variant (mutant) frequencies (Vf) of female mice (three per group) were 7.2 x 10(-6) at 0 ppb; 29.2 x 10(-6) at 40 ppb; 62.5 x 10(-6) at 100 ppb and 25.0 x 10(-6) at 1000 ppb. The Vf of unexposed mice housed in standard cages was 13.2 x 10(-6). In male mice the same pattern of response was observed, but the increases in Vf in response to benzene were not as great. In both sexes of mice, the increases at 40 and 100 ppb were significantly greater than at 0 ppb (P less than 0.05). The increase in Vf with exposure to 100 ppb and the decline at 1000 ppb parallel the results observed for chromosome damage in spleen lymphocytes from the same animals (Au et al., Mutation Res., 260 (1991) 219-224). These results indicate that sub-chronic exposure to benzene at levels below the current Occupational Safety and Health Administration Permitted Exposure Limit may induce gene mutations in lymphocytes in mice.

Administration, Inhalation↗

PubMed1992

Enhanced suppression of humoral immunity in DBA/2 mice following subchronic exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD).

Previous studies have indicated that mice which differ in their acute susceptibility to responses mediated by the Ah receptor have a pattern of suppression of the antibody response which is consistent with a role by the putative dioxin receptor. The objective of the present investigation was to compare the TCDD-induced suppression of the antibody response following acute and subchronic exposures in B6C3F1 mice, an Ah-high-responder strain, and DBA/2 mice, an Ah-low-responder strain. Results of our initial studies demonstrate that suppression of humoral immunity can be enhanced in DBA/2 mice approximately 10-fold following subchronic versus acute exposures to the same cumulative doses of TCDD. This change in suppression of the antibody response in DBA/2 mice was not accompanied by significant changes in liver weight (hepatomegaly), as was observed in the B6C3F1 strain when exposed under comparable conditions. In contrast, effects on thymus weight (involution) were enhanced in the DBA/2 mice following subchronic exposure and demonstrated a higher degree of atrophy than was seen in the B6C3F1 strain (68 versus 56% decrease in thymic weight at the 42 micrograms/kg cumulative dose). These findings suggest that multiple mechanisms may be operating to suppress humoral immunity in vivo and that the conditions of exposure can alter the toxic effects of TCDD in the DBA/2, Ah-low responsive, mouse strain.

Animals↗

PubMed1992

Evaluation of the genotoxic effects of a folk medicine, Petiveria alliacea (Anamu).

Crude extract from a plant known as Petiveria alliacea (Anamu) is used extensively as folk medicine in developing countries like Colombia, South America. Although the plant is known to contain toxic ingredients potential adverse health effects from its use have not been adequately evaluated. We investigated its genotoxic activities by conducting a sister chromatid exchange (SCE) assay using cells in vitro and in vivo. Lymphocytes from humans were treated at 24 h after initiation of culture for 6 h with alcohol extract from the folk medicine. Concentrations of 0, 10, 100, 250, 275, 500, 750, and 1000 micrograms/ml of the extract were used. Significant dose-dependent increase of SCE (3.7-7.4 SCE per cell) were observed (analysis of variances, p less than 0.01). Delay in cell proliferation but not inhibition of mitosis was also observed. In another experiment, mice were exposed once orally to 1x, 200x, 300x and 400x the human daily consumption dose of Anamu. The induction of sister chromatid exchanges in bone marrow cells were investigated. We observed a significant dose dependent increase of SCE compared with the saline control (2.15-4.53; p less than 0.01) and compared with the solvent control (3.04-4.53; p less than 0.01). Our data suggest, therefore, that the folk medicine contains mutagenic and potentially carcinogenic agents although the medicine is not a potent mutagen. Individuals who consume large amounts of this drug may be at risk for development of health problems. Further studies with cells from exposed individuals and from experimental animals should be conducted to provide a better evaluation of health risk from the use of this drug.

Animals↗

PubMed1992

Inhibition of gastrin-stimulated growth of gastrointestinal tumour cells by octreotide and the gastrin/cholecystokinin receptor antagonists, proglumide and lorglumide.

The rat pancreatic cell line, AR42J possessed high-affinity gastrin and somatostatin receptors and its growth was stimulated by physiological gastrin-17 concentrations between 5 x 10(-11) mol/l and 10(-9) mol/l as measured by [75Se]selenomethionine uptake. The somatostatin analogue, octreotide (2 x 10(-7) to 2 x 10(-11) mol/l), reduced this stimulated growth. Gastrin-stimulated AR42J growth was also inhibited by proglumide (3 x 10(-4) mol/l) and lorglumide (3 x 10(-5) mol/l) at maximal G17 concentrations of 5 x 10(-11) and 10(-10) mol/l, respectively, and the analogues competed with [125I] gastrin-17 (5 x 10(-10) mol/l) for binding to gastrin receptors on AR42J (50% inhibitory concentrations, less than or equal to 10(-3) mol/l and 4 x 10(-6) mol/l, respectively. Octreotide reduced the basal growth of the human gastric cell line, MKN45G, (which is associated with intracellular gastrin immunoreactivity) in serum-free medium to 73% of control at a concentration of 2 x 10(-8) mol/l, which was reversed by gastrin-17 (10(-10) mol/l). Lorglumide (3 x 10(-5) mol/l) also reduced the basal growth to 30% of control, which was reversed to 78% by 10(-5) mol/l gastrin. Proglumide had no effect on the basal growth of MKN45G.

Animals↗

PubMed1992

Therapeutic effect of the gastrin receptor antagonist, CR2093 on gastrointestinal tumour cell growth.

The gastrin receptor antagonist, CR2093, competed with 125I-gastrin-17 (5 x 10(-10) M) for binding to gastrin receptors on the rat pancreatic adenocarcinoma, AR42J (CR2093 concentration inducing 50% of 125I-gastrin-17 binding (IC50) was 8 x 10(-5) M), on the human gastric adenocarcinoma, MKN45 (IC50 5.5 x 10(-5) M) and the human colo-rectal adenocarcinoma C523 (IC50 greater than 10(-4) M). Intravenous administration of CR2093 (40 mg kg-1 day-1) reduced the gastrin-17 stimulated growth of AR42J xenografts in nude mice to below that of the original basal growth (P = 0.0166 from basal and P = 0.0109 from gastrin stimulated growth). CR2093 administration also reduced the gastrin-stimulated growth of MKN45 xenografts (P = 0.045) but failed to inhibit the gastrin enhanced proliferation of C523 xenografts. This may be related to the affinity (Kd) of the gastrin receptors present on the xenograft lines as the Kds of the two xenografts inhibited by CR2093 were 4.6 x 10(-10) M (AR42J) and 1.2 x 10(-9) M (MKN45) respectively whereas the Kd of C523 was of higher affinity (2.2 x 10(-10) M). GR antagonists may be a viable therapeutic option for gastrin receptor positive, gastro-intestinal tumours.

Amino Acids↗

PubMed1992

Highly purified human alpha-thrombin promotes morphological transformation of BALB/c 3T3 cells.

Purified human alpha-thrombin stimulates phosphoinositide turnover as a necessary step in its stimulation of fibroblast cell proliferation. Since phosphoinositide turnover releases diacylglycerol, which activates protein kinase C, we postulated that long-term exposure to thrombin might promote cellular transformation in a manner similar to long-term exposure to phorbol esters, which also activate protein kinase C. The present studies show that chronic exposure of BALB/c 3T3 cells (subclone A31-1-13) to thrombin (5 micrograms/ml) led to a 4- to 20-fold increase in the frequency of morphological transformation over controls as determined by induced foci in monolayer cultures. The foci appeared to represent true transformants as cells from randomly selected foci grew in soft agar and had saturation densities 2- to 3-fold higher than control cells. Acute thrombin treatment for 24 h resulted in small but statistically significant (P less than 0.05) increases in morphological transformation with or without promotion by phorbol myristate acetate, indicating that thrombin can act as a weak initiator or complete carcinogen in this test system. Initiation of cells with low levels of 3-methylcholanthrene followed by promotion with thrombin caused a greater enhancement of morphological transformation (P less than 0.005). Thus, it appears that most of the stimulation of in vitro cell transformation by thrombin may be due to its promotional activity. These results raise the possibility that thrombin released locally following tissue injury or chronic irritation may play a role in cellular transformation and tumor development, especially in tissues sensitized by exposure to initiating carcinogens.

3T3 Cells↗

PubMed1992

Laser Doppler flowmetry in evaluation of cutaneous wound blood flow using various suturing techniques.

Measurements of blood flow on either sides of abdominal incisions and of uninjured control skin in 63 patients with three kinds of suturing techniques (clips in 21 patients, mattress in 21 patients, and subcuticular suture in 21 patients) on the 1st and 5th postoperative day were made, using an infrared laser Doppler flowmeter. There was a significantly higher flow on the 1st versus the 5th postoperative day. There is statistically higher blood flow in wounds sutured with subcuticular sutures in comparison with the two other groups. The method may allow the relationship of blood flow to wound healing to be evaluated.

Abdominal Muscles↗

PubMed1992

Percutaneous ultrasound guided cholecystostomy with double bubble catheter.

We have used a prototype double bubble cholecystostomy catheter in four very ill patients. This has been done under local anaesthetic using a Seldinger technique, ultrasound guidance, and a trans-peritoneal approach to the gallbladder. The catheter provides drainage, cholangiography, and is intended to allow instrumentation of the biliary tract at a later stage.

Aged↗

PubMed1992

Colorectal cancer screening: optimal compliance with postal faecal occult blood test.

Five approaches to postal faecal occult blood test (FOBT) were compared in a population sample of 966 subjects collected from three general practitioner patient lists in Southern Sydney. The highest compliance rate (59.8%) was achieved by a method using a general practitioner letter, with no dietary restrictions with FOBT. This was also the least expensive method. Compliance rates can be affected by incorrect address information and screenees not considering themselves to be current patients. An explanation from the family doctor addressed personally to the patient with an enclosed FOBT kit can achieve high compliance rates.

Aged↗

PubMed1992

Effect of electrohydraulic and extracorporeal shock waves on gastrointestinal cancer cells and their response to cytotoxic agents.

Electrohydraulic and extracorporeal shock waves were used to treat the colorectal and gastric cancer cell lines LIM 2412 and MKN45. The effect on viability, cell proliferation, and the action of antitumour drugs was studied. Results showed that electrohydraulic and extracorporeal shock waves were cytotoxic to all cell lines and also caused considerable inhibition of cell proliferation. A significant additional reduction in cell viability was achieved by shock waves in cancer cells treated with methotrexate, 5-fluorouracil, and vincristine. These data indicate that shock waves may be worthy of further evaluation in the treatment of gastrointestinal cancers.

Cell Survival↗

PubMed1992

Anaesthetic experience with cryotherapy for treatment of hepatic malignancy.

Hepatic cryotherapy is a relatively new technique, currently employed in the treatment of unresectable liver malignancy, which involves direct freezing of tumour deposits with liquid nitrogen. In a review of 26 patients undergoing this procedure, the anaesthetic considerations are defined. The total operation time ranged from 133 to 410 minutes. In spite of preventative measures, varying degrees of hypothermia occurred (range 33.7 degrees C to 36.5 degrees C), but no sequelae were encountered. Mean blood loss was 926 ml, and eleven patients required blood transfusion of between one and five units. There was a marked drop in platelet count associated with cryotherapy (mean fall of 123,000/mm3 by the second postoperative day). Following the procedure, fever and basal pulmonary atelectasis were common, while hypoglycaemia and renal impairment occurred on single occasions. Six patients underwent postoperative mechanical ventilation. Despite this, the mean hospital stay was under seven days.

Adult↗

PubMed1992

Somatostatin receptors in human colorectal cancer.

We have previously reported that somatostatin may reduce tumour cellular proliferation in patients with colorectal carcinoma. However, it is not known what proportion of primary colorectal cancers express somatostatin receptors. We have therefore evaluated somatostatin receptor status in 50 primary colorectal cancers. Twelve (24%) of the cancers were shown to be somatostatin receptor positive. There was no correlation between receptor status and tumour stage or grade.

Autoradiography↗

PubMed1992

Serum gastrin concentrations in colorectal cancer patients.

Fasting serum gastrin concentrations were shown to be elevated in colorectal cancer patients compared with controls (P = 0.0037), which was mainly accounted for by a subgroup of patients who had significantly elevated levels. In cancer patients there was no difference in gastrin concentrations in blood taken from a tumour-draining mesenteric vein and from a peripheral vein at the time of colonic resection. Serum gastrin concentrations were significantly lower after apparently curative resection for colorectal cancer (P = 0.028), suggesting that the elevated serum gastrin seen in these patients may be due, at least in part, to secretion of gastrin by the tumour.

Adult↗

PubMed1991

Intracellular gastrin in human gastrointestinal tumor cells.

Flow cytometry and immunohistochemical analyses of the human gastric adenocarcinoma cell line MKN45G identified an intracellular peptide recognized by an anti-gastrin-17 (G17) antiserum but not by an anti-cholecystokinin-specific antiserum. Staining was not associated with the parental line MKN45, of which MKN45G is a clonal variant. The MKN45G cell line had elevated in vitro growth in serum-free medium in which the proliferation of MKN45G cells but not MKN45 cells was reduced to 58% of the control value by treatment with a rabbit anti-G17 antiserum. This inhibition of proliferation was reversed by preabsorbing the antiserum with excess G17. Disaggregated primary human gastric and colorectal tumors were screened for gastrin immunoreactivity by flow cytometry, and 6 of 28 colorectal and 8 of 22 gastric tumors had greater than 20% positively staining cells.

Adenocarcinoma↗